Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

👉20-25% of Graves’ patients have orbitopathy. While usually mild, 5% have moderate to severe disease.

👉Disease activity is assessed using a clinical activity score.

👉A score ≥3 is classified as active and more likely to respond to immunomodulatory therapy such as corticosteroids.

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👉After a rapid rise in thyroid cancer rates in the United States over nearly 30 years, the steady climb tapered from 2009 to 2014 and has appeared to be stable ever since, new research shows.

👉Between 2009 and 2016, after three decades of rapid increase, the incidence of thyroid cancer incidence in the United States reached a plateau and possibly started to decline.

👉Although a true decline in the occurrence of thyroid cancer is a possible explanation for these changing trends, less intensive workup of thyroid nodules is more likely.

👉From 1974 to 2013, the incidence of thyroid cancer in the United States tripled, from 4.5 to 14.4 cases per 100,000 in the population.

👉Although other factors have not been ruled out, the unprecedented rise in incidence is widely believed to have resulted from the advent of newer imaging technologies capable of detecting smaller, subclinical thyroid cancers that are of low risk.

👉The new finding that incidence rates have leveled off reflects a trend that has been happening for some time in which there has been an evolving understanding of overdiagnosis and the indolent nature of many small thyroid cancers.

👉Studies of autopsies have shown that clinically occult thyroid cancers are detected in 4% to 11% of people who have no known thyroid disease, underscoring the fact that small thyroid cancers are commonly inconsequential, they note.

👉The appreciation of the indolent nature of many thyroid cancers was reflected in changing clinical practice guidelines, including recommendations against screening for thyroid cancer by the US Preventive Services Task Force in 2017.

👉Other changes in guidelines include radiographic classification systems for thyroid nodules that have been implemented by several US professional societies and recommendations that the routine use of biopsy of nodules be more closely stratified according to risk.

👉In 2009 and 2015, for example, American Thyroid Association guidelines introduced size- and appearance-based criteria and recommended observation rather than immediate biopsy for many smaller, lower-risk nodules, the authors note.

👉Trends in other countries offer more extreme examples of the effects of thyroid screening, the authors state. In South Korea, the widespread practice of screening healthy individuals with thyroid ultrasound corresponded with a surge in thyroid cancer incidence to a level 15 times greater in 2011 than in 1993.

👉Subsequently, upon awareness of the likely role of thyroid screening processes in the trend and a significant revision of screening practices, thyroid cancer incidence rates in South Korea reversed.

👉For the study, Marti and colleagues analyzed data from the population-based Surveillance, Epidemiology, and End Results (SEER) 13 registry, representing 14% of the US population in 13 geographic regions.

👉They found an age-adjusted increase in thyroid cancer incidence from 5.7 to 13.8 per 100,000 individuals from 1992 to 2009. The highest annual percentage change, 6.6% (95% confidence interval [CI], 6.2% – 7.0%), occurred from 1998 to 2009.

👉Subsequently, a significant slowing, from 13.8 to just 14.7 per 100,000, occurred from 2009 to 2014 (annual percentage change, 2.0%; 95% CI, 0.3% – 3.7%; P = .001).

👉Since 2014, the incidence has remained stable, and there has even been a slight decline, from 14.7 to 14.1 cases per 100,000 (annual percentage change, –2.4%; 95% CI, –7.5% to 3.1%; P = .06).

👉With regard to subcentimeter thyroid cancers, which are believed to have largely driven the higher overall incidence rates, the authors found an expectedly larger increase in rate. From 1992 to 2009, the rate of subcentimeter cancers increased from 1.2 to 4.7 per 100,000; the highest annual percentage change occurred from 1996 to 2009 (9.1%; 95% CI, 8.4% – 9.8%).

👉That increase in subcentimeter cancers stabilized from 2009 to 2013, with an incidence of 4.7 to 5.3 per 100,000, for an annual percentage change of just 2.9% (95% CI, −2.5% to 8.6%; P = .02).

👉Further decline in subcentimeter thyroid cancers was observed from 2013 to 2016, from 5.3 to 4.7 per 100,000 (annual percentage change −3.7%; 95% CI, −8.7% to 1.7%; P = .04).

👉The patterns reflect not only the increasing ability to detect smaller cancers but also the subsequent awareness of the implications, the authors note.

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👉What’s the difference between cure, persistent disease and recurrent disease? Cure after parathyroidectomy is defined as the return of normal calcium homeostasis for a minimum of 6 months

👉TheAAES guidelines https://jamanetwork.com/journals/jamasurgery/fullarticle/2542667

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👉A radioactive iodine uptake scan can sometimes be used to help in determining the cause of hyperthyroidism. In Graves’ disease, there is diffuse increased uptake throughout the gland (image B)

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👉While thyroid cancer is infrequent in Graves’ disease (≤2%), thyroid nodules discovered during the work-up of Graves’ should be managed per published guidelines such as those of the American Thyroid Association. (ncbi.nlm.nih.gov/pmc/articles/PMC4739132/pdf/thy.2015.0020.pdf)

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👉Thyroidectomy for Graves’ disease can be challenging.

👉If surgery is chosen as primary therapy for Graves’ disease, the patient should be referred to a high-volume thyroid surgeon.

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December 13, 2019—San Antonio, Texas—The use of estrogen alone as menopausal hormone therapy has been shown to decrease breast cancer incidence and death with persistent results after discontinuation of use. Estrogen plus progestin increased breast cancer incidence with persistent results after discontinuation of use.

This outcome of the long-term follow-up of two large, randomized, placebo-controlled Women’s Health Initiative trials in postmenopausal women was reported at the 2019 San Antonio Breast Cancer Symposium (SABCS), from December 10 – 14.

Rowan T. Chlebowski, MD, PhD, of the Harbor-University of California, Los Angeles Medical Center, explained that treatment with estrogens and progestin led to significantly increased breast cancer incidence in these trials involving 27,347 postmenopausal women.

Dr. Chlebowski explained that these adverse effects were seen even 10 years following discontinuation of treatment. In contrast to numerous findings from observational studies over decades, estrogen alone led to significantly reduced breast cancer incidence and breast cancer-related deaths.

According to Dr. Chlebowski, these benefits were seen 10 years after discontinuing treatment. Although patient characteristics differed between the observational studies and the Women’s Health Initiative randomized trials, the findings regarding estrogen use alone are difficult to reconcile.

Dr. Chlebowski and colleagues updated earlier findings of two randomized Women’s Health Initiative clinical trials on breast cancer incidence and breast cancer mortality in women randomized to estrogen + progestin, estrogen alone, or placebo after more than 19 years of cumulative follow-up.

They enrolled postmenopausal women aged 50 to 79 years with no prior breast cancer in one of two randomized clinical trials at 40 US centers from 1993 to 1998 and followed them through September 2016.

Postmenopausal women with an intact uterus received estrogen + progestin (n = 8506) or placebo (n = 8102) for a median of 5.6 years. Postmenopausal women who had undergone hysterectomy received estrogen alone (n = 5310) or placebo (n = 5429) for a median of 7.2 years.

After 16.1 years of cumulative follow-up, among those who received estrogen alone, 520 incident breast cancers occurred during the post-intervention period.

Compared with women who had received placebo, those who had received estrogen were 27% less likely to have been diagnosed with breast cancer and 44% less likely to die of the disease.

These positive outcomes are in agreement with earlier findings of this trial during the intervention period. After 18.3 years of cumulative follow-up, among those who received estrogen + progestin acetate, 1003 incident breast cancers occurred during the post-intervention period.

Compared with women who had received placebo, those who had received estrogen + progestin were 29% more likely to have been diagnosed with breast cancer. This negative outcome is in agreement with the earlier finding of this trial during the intervention period.

Estrogen + progestin was associated with an increased risk of death from breast cancer in the extended analysis, but the difference did not reach statistical significance.

Dr. Chlebowski explained that millions of women around the world continue to receive hormone therapy with estrogen + progestin (for menopausal women with an intact uterus) or estrogen alone (for menopausal women who underwent hysterectomy).

He also noted that the influence of hormone therapy for menopausal women on breast cancer incidence and mortality remains unsettled after nearly 50 years, with discordant findings from randomized clinical trials and observational studies.

According to Dr. Chlebowski, the Collaborative Group on Hormonal Factors in Breast Cancer published a meta-analysis of 58 observational studies earlier this year, demonstrating that treatment with estrogen + progestin or estrogen alone were associated with significantly increased risk of breast cancer incidence. Additionally, treatment with estrogen + progestin or estrogen alone were associated with significantly increased breast cancer mortality in the Million Women Study.

Key limitations of the study include that breast cancer mortality analyses were not protocol-specified. Death from breast cancer is the most clinically relevant breast cancer outcome, however. In addition, the trials evaluated one dose and schedule of estrogen + progestin or estrogen alone, respectively. Findings may not apply to other preparations, doses, or schedules.

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December 12, 2019—San Antonio, Texas—A 10-year follow-up study of patients with breast cancer who had been treated with accelerated partial breast irradiation after surgery showed that their rates of recurrence were similar to those of patients who had received whole breast irradiation.

This outcome of the randomized, phase III Accelerated Partial Breast Irradiation Intensity Modulated Radiotherapy (APBI IMRT) trial was reported at the 2019 San Antonio Breast Cancer Symposium (SABCS), from December 10 – 14.

Icro Meattini, MD, of the University of Florence, Italy, explained that there were no differences in patient outcomes among selected cases, whether they were treated with whole breast irradiation or accelerated partial breast irradiation. Improved quality of life, reduced toxicity, and potential reductions in overall treatment times may result from a once-daily regimen of external accelerated partial breast irradiation.

According to Dr. Meattini, accelerated partial breast irradiation is less expensive and may be less likely to contribute to cosmetic changes compared with whole breast irradiation. Partial breast irradiation is an effective method for de-escalation of breast cancer treatment. Dr. Meattini suggested that partial breast irradiation provides a cost-effective, safe, and efficacious treatment option for many patients.

Dr. Meattini and colleagues examined 10-year follow-up data for women enrolled in APBI IMRT. The 5-year follow-up showed no significant difference in tumor recurrence or survival rates. APBI IMRT enrolled 520 women >40 years of age who suffered from either stage I or II breast cancer. Between 2005 and 2013, patients were randomized 1:1 to either accelerated partial breast irradiation or whole breast irradiation.

Patients in the accelerated partial breast irradiation arm received a total of 30 Gray (Gy) of radiation to the tumor bed in five daily fractions. Those in the whole breast irradiation arm received a total of 50 Gy in 25 daily fractions to the whole breast, plus a boost of 10 Gy to the tumor bed in five daily fractions.

Both treatment arms were comparable in terms of age, tumor size, tumor type, and adjuvant endocrine treatment, and both achieved a median 10-year follow-up.

The majority of patients harbored hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, and most were over age 50 years.

After 10 years, 3.3% of patients in the accelerated partial breast irradiation group had experienced a recurrence of breast cancer vs 2.6% in the whole breast irradiation group. These results were comparable to the 5-year results, in which the group who received accelerated partial breast irradiation experienced a 2.4% recurrence rate, and patients who received whole breast irradiation, a 1.2% recurrence rate.

Differences were not statistically significant for either. Overall survival at the 10-year mark was also very similar between the two groups: 92.7% among women who had received accelerated partial breast irradiation and 93.3% among women who received whole breast irradiation.

Breast cancer-specific survival was 97.6% among patients who received accelerated partial breast irradiation; 97.5% among those who received whole breast irradiation. The rate of distant metastasis-free survival was 96.9% among both women who received accelerated partial breast irradiation and those who received whole breast irradiation.

Although the results were close, whole breast irradiation proved slightly more effective in reducing recurrence rates. The results suggested that the less invasive partial breast procedure may be an acceptable choice for patients with early breast cancer.

Dr. Meattini explained that many patients diagnosed with early breast cancer undergo lumpectomy followed by a course of radiation. He noted that postoperative radiation remains a primary adjuvant treatment for breast cancer that leads to significant reductions in the rate of local relapse occurrence.

Partial vs whole breast radiation has been a topic of multiple clinical trials. In recent years, researchers have sought to determine whether accelerated partial breast irradiation might be as effective as whole breast irradiation in preventing recurrence.

The growing body of research may help clinicians recommend that patients at lower risk of recurrence choose accelerated partial breast irradiation, whereas those at a higher risk of recurrence be recommended for whole breast irradiation.

Dr. Meattini concluded that these findings support promising results from prior studies demonstrating excellent disease control following accelerated partial breast irradiation.

The study’s chief limitation is its relatively small size.

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• The technique of subtotal thyroidectomy:
  • Relied on the anatomical removal of visibly abnormal thyroid tissue.
  • Leaving behind bilateral posterior remnants.
• The move to total thyroidectomy has meant not only that more thyroid tissue is  removed, but that rather there has been a progressive awareness of the vagaries of embryological development of the thyroid, with dissection now focused on those changes in order to ensure completeness of resection, and thus efficacy of the procedure.
• Thyroid development involves the midline descent of thyroid tissue from the foramen caecum to the level of the larynx along the thyroglossal tract, at which stage the left and right lobes develop:
  • What is not as well appreciated is that thyroid descent may well continue into the thyrothymic region (and even into the anterior mediastinum) forming a prolongation of thyroid tissue or even completely separate thyrothymic thyroid rests.
• In addition the lateral thyroid component arising from the 4th branchial cleft and ultimobranchial body fuses with the median component:
  • To form the tubercle of Zuckerkandl:
    • A distinct anatomical structure:
      • This fusion is not only the source of the thyroid’s C-cells, but is also essential in the process of follicular development.
• Thyroglossal tract and pyramidal remnants:
  • Routine dissection of the pyramidal area up to the laryngeal cartilage should be part of every total thyroidectomy:
    • Even minimal recurrence in this area can be very apparent to the patient.
    • More importantly, in patients with Graves’ disease:
      • A small pyramidal lobe remnant can contain sufficient thyroid tissue to cause clinical recurrence even after an apparent ‘total’ thyroidectomy.
  • Thyrothymic thyroid rests:
    • Thyrothymic thyroid rests are present in over 50% of patients (if looked for), although most are small.
    • They are often mistaken for small lymph nodes, or even parathyroid glands, and mostly cause no real problems.
    • They are classified according to the nature of their connection to the thyroid gland proper:
      • Grade I:
        • Is a protrusion of thyroid tissue from the lower edge of the thyroid lobe.
      • Grade II:
        • Is a thyroid rest connected by a bridge of thyroid tissue
      • Grade III:
        • Is connected by only a fibrovascular core.
      • Grade IV:
        • Has no connection at all with the thyroid proper.
    • Their clinical significance lies in the fact that, if not removed at the initial operation, they may well reappear as retrosternal recurrence after apparent ‘total’ thyroidectomy:
      • Routine dissection of the thyrothymic area down to the thoracic inlet looking for such rests should therefore be part of every total thyroidectomy.
• The tubercle of Zuckerkandl:
  • This structure, first described by Zuckerkandl in 1902, is a distinct anatomical entity, and can be found in nearly two-thirds of patients undergoing thyroid surgery.
  • It is classified according to size (grades 0 to grade 3) using a system developed by Pelizzo et al.
  • The tubercle of Zuckerkandl is often the source of local pressure or obstructive symptoms, especially when the thyroid itself is relatively small.
  • The importance of the tubercle of Zuckerkandl, once again, is that if not looked for and removed during thyroid surgery:
    • It may be a source of persistent unrelieved symptoms or recurrence.
  • An understanding of the anatomy of the tubercle of Zuckerkandl is also central to safe surgical dissection:
    • It usually enlarges lateral to the RLN, with the nerve appearing to pass into a cleft medial to it:
      • A situation that some surgeons used to describe as the nerve passing into the thyroid substance.
  • Early elevation of the tubercle of Zuckerkandl usually allows the recurrent nerve to be easily and safely ‘encountered’ even though not initially visible.
  • However:
    • An uncommon but high risk situation is where the RLN runs lateral to an enlarged tubercle of Zuckerkandl, placing it at increased risk of damage during dissection.
  • Another important point is that the normal superior parathyroid gland, also being derived from the fourth branchial cleft, is commonly found in close association, cephalad to the tubercle of Zuckerkandl.

¿Quién debe realizar cirugía de tiroides?

•  Su entrenamiento es el siguiente:

  • Tumores de Cabeza y Cuello / Cirugía Endocrina:_
    • Fox Chase Cancer Center

• Tumores de Cabeza y Cuello / Cirugía Endocrina:
  • IFHNOS / Memorial Sloan Kettering Cancer Center

 

• Cirugía Oncológica Compleja:
  • Fox Chase Cancer Center

 

• Cirugia General y Gastrointestinal:
  • Michigan State University

• Maestría en Ciencias de Investigación:
  • Drexel University

• El Dr. Arrangoiz es:
  • Fellow del Colegio Americano de Cirugía

 

• El Dr. Arrangoiz es:
  • Fellow de la Sociedad de Cirugia Oncológica:

👉If surgery is chosen as primary therapy for Graves’ disease, near-total or total thyroidectomy (rather than subtotal thyroidectomy) is the procedure of choice.

👉ATA guidelines https://www.liebertpub.com/doi/pdfplus/10.1089/thy.2016.0229

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